hypericum and Pulmonary-Fibrosis

Some proteases involved in extracellular matrix degradation are instrumental not only in overcoming tissue barriers to allow normal extravasation of hematic cells, but also in facilitating pathological processes such as inflammation, angiogenesis and tumor invasion. The possibility of blocking these enzymes has led to the development of synthetic inhibitors, though clinical trials have been disappointing owing to considerable side effects. However, long before enzymes were first isolated, these same pathologies were being treated in plant-based folk remedies, and today science is screening them for their reputed beneficial effects.. We present studies of 2 vegetable components as protease inhibitors. The first, (-)epigallocatechin-3-gallate - from green tea, has proved a good weapon for inhibiting gelatinases MMP-2 and MMP-9, but an even better inhibitor of leukocyte elastase (LE) activity; in vivo it blocks inflammation, angiogenesis and tumor invasion. The second, hyperforin - from Hypericum sp, inhibits LE-triggered activation of MMP-9, PMN chemotaxis and chemoinvasion, PMN-triggered angiogenesis, and inflammation-triggered pulmonary fibrosis; it also represses tumor-cell expression of MMP-2, thereby restraining invasion and metastasis.. Modern research clearly vindicates epidemiological and historical evidence of the beneficial effects of two long-used allies from the plant kingdom, going a step beyond by shedding light on mechanistic keys.

Topics: Animals; Anti-Inflammatory Agents; Bridged Bicyclo Compounds; Catechin; Humans; Hypericum; Matrix Metalloproteinases; Neovascularization, Pathologic; Phloroglucinol; Pulmonary Fibrosis; Tea; Terpenes

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis and limited therapies, and transforming growth factor-β1 (TGF-β1) plays a central role in the pathogenesis of IPF. Here, we aimed to investigate the chemical constituents and biological activities of Hypericum longistylum and detect whether the isolated compounds inhibit the TGF-β1/Smad3 signaling pathway to identify candidate compounds for the treatment of pulmonary fibrosis. Fifteen compounds (1-15) were isolated from H. longistylum and their structures were elucidated on the basis of spectroscopic analyses. An in vitro MTT assay was used to test the effect of these fifteen compounds on fibroblast cytotoxicity and vitality. Furthermore, their bioactivities were screened using a TGF-β1/Smad3 pathway luciferase reporter in vitro. MTT screening found that compounds 1-15 had no deleterious effects on normal mouse lung fibroblasts and no significant inhibition of vitality. Luciferase assay showed that compounds 14 and 15 could significantly inhibit the TGF-β1/Smad3 pathway with the inhibition rates of 67.92% and 93.10%, respectively. Both compounds can be used as lead compounds for structural modification and optimization to obtain more drug candidates for the treatment of pulmonary fibrosis.

Topics: Animals; Antifibrinolytic Agents; Cell Survival; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fibroblasts; Hypericum; Mice; Molecular Structure; Plant Extracts; Pulmonary Fibrosis; Signal Transduction; Smad3 Protein; Structure-Activity Relationship; Transforming Growth Factor beta1